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Dynamic change of the CENP-C-centromere interaction is regulated by CDK1

渡邉, 励人 大阪大学 DOI:10.18910/82345

2021.03.24

概要

To maintain correct genetic information, the genome should be certainly replicated and equally segregated into daughter cells through the cell cycle progression. The kinetochore is essential structure for faithful chromosome segregation during mitosis. To form a functional kinetochore, constitutive-centromere-associated-network (CCAN) proteins are assembled on the centromere chromatin that contains centromere-specific histone H3 variant, CENP-A. CENP-C—a CCAN protein—directly interacts with the CENP-A containing nucleosome (CENP-A nucleosome) to nucleate the kinetochore structure. As CENP-C is a hub protein for kinetochore assembly, it is critical to address how the CENPA-CENP-C interaction is regulated during the cell cycle progression. To address this question, I investigated the CENP-C C-terminal region including a conserved CENP-Abinding motif in both chicken and human cells, and found that CDK1-mediated phosphorylation of CENP-C facilitates its binding to CENP-A in vitro and in vivo. I observed that the CENP-A binding is related to CENP-C kinetochore-localization and functions during mitosis in chicken DT40 cells. We also demonstrated that the CENP-ACENP-C interaction is critical for long-term viability in human RPE-1 cells. These results provide deeper insights into protein-interaction network plasticity in centromere proteins during cell cycle progression.

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